The overall goal of this research proposal is to study the emergence of HIV drug resistance (HIVDR) in a population beginning first-line antiretroviral therapy (ART) and assess potentially related factors at one ART roll-out site in Hanoi, Vietnam: The National Institute of Infection and Tropical Disease (NIITD). Importantly, the project will lead to the development of new allele-specific PCR assays for the detection of important HIVDR mutations present at low frequency prior to the start of ART and will develop a powerful model to define the virologic impact of low level HIVDR mutations in individuals starting first-line ART. To achieve these goals, I will use a newly established cohort of HIV infected adults in Hanoi, Vietnam. In 2005, my mentor Dr. Christine Wanke of Tufts University along with her collaborator Dr. Nguyen Due Hien from the National Institute of Infection and Tropical Disease (NIITD) in Hanoi, Vietnam established a cohort of 300 HIV-1 seropositive individuals. Dr. Wanke's project, entitled "Nutritional Status of HIV-positive and HIV- negative drug users (IDUs) in Hanoi, Vietnam" [Center for Metabolic Research on HIV and Drug Use;NIH grant 1 P30 DA 13868] is a prospective cohort study that will follow subjects over a period of two years with study visits at six-month intervals. My proposal provides a critically important translational virology component to the existing study and is embedded in the parent study. The study will provide new and important insight into the emergence of HIVDR and will serve to identify factors associated with the emergence of HIVDR at this Vietnamese ART delivery site. Although the results will be site-specific, factors identified to be associated with the emergence of HIVDR at this site may be qualitatively generalized to other ART delivery sites. Additionally, this project will lead to the development of new allele-specific PCR assays for the detection of low-frequency HIVDR mutations and will develop a model to study the impact of these mutations on viral suppression after 12-months of first line ART. The results of this model are anticipated to be of importance in advancing the understanding of the development of HIVDR and in understanding the impact of low-frequency HIVDR mutations present at baseline on successful treatment outcomes. Importantly, the model developed as part of this study may be applied to other populations both in developed and resource-limited countries to understand the impact of low-frequency HIVDR mutations on successful ART treatment outcomes.